According to the US Department of Health and Human Services, healthcare-associated infections (HAI), such as catheter-associated bloodstream and urinary tract infections, ventilator-associated pneumonia, and surgical site infections, are among the leading causes of hospital deaths in the US, accounting for 1.7 million infections and 99,000 associated deaths in 2002. [1,2] Treating HAI translates to increases in the cost of patient care. For example, it is estimated that HAI incur an estimated $28-33 billion in excess healthcare costs each year [1]. Catheter-associated urinary tract infections (CAUTI) are the most common HAI, representing more than 30% of HAI reported by acute care hospitals [3]. This translates into >560,000 infections annually, with an attributable mortality rate of 2.3% (>13,000 deaths) [3]. In addition to UTI-attributable deaths, CAUTI are the leading cause of secondary healthcare-associated bloodstream infections, which have a mortality rate of 10% [4]. Overall, CAUTI significantly increase patient morbidity, increasing hospital stays and costs of patient care [5-8]. Catheter-associated microbes are also thought to be one of the largest reservoirs of nosocomial antibiotic-resistant pathogens [9, 10].
Most CAUTI develop when bacteria from a variety of sources colonize the urinary catheter [11-13]. Upon attaching to surfaces of the device, bacteria proliferate and form aggregates within a complex matrix consisting of extracellular polymeric substances, typically polysaccharides and polypeptides [15]. This mass of attached bacteria and the associated extracellular polymeric substances is commonly referred to as a biofilm or slime [63]. Antibacterial agents have difficulty penetrating biofilms and killing and/or inhibiting the proliferation of the bacteria within the biofilm [64]. The colonization of the bacteria on and around the device and the synthesis of the biofilm barrier may eventually result in encrustation, occlusion and failure of the device. The biofilm itself also serves as a sanctuary for pathogens, particularly bacterial pathogens including gram positive bacteria (such a Staphylococcus species and Enterococcus species), and gram negative bacteria (such as Enterobacter species and Pseudomonas species).
Biofilm-associated organisms may elicit disease processes by detachment of individual cells or aggregates of cells resulting in bloodstream or urinary tract infections, by production of endotoxin, or by providing a niche for the development of antimicrobial-resistant organisms. One example of a pathogen associated with CAUTI is Staphylococcus aureus. Both S. aureus and coagulase-negative staphylococci (for example, S. epidermidis) have emerged as major nosocomial pathogens associated with biofilm formation on implanted medical devices [65;66]. These organisms are among the normal carriage flora of human skin and mucous membranes, making them prevalent complications during and after invasive surgery or prolonged hospital stays. As bacteria carried on both healthy and sick people, staphylococci are considered opportunistic pathogens that invade subjects via open wounds and via implanted medical devices.
Several approaches for delaying CAUTI biofilm development have been investigated but no effective strategy has been established. Because biofilm organisms are highly tolerant to antimicrobial agents, infections associated with indwelling catheters often do not respond to systemic drug therapy. Instillation of the catheter retention balloon with bactericidal chemicals may introduce high enough local concentrations to significantly inhibit biofilm formation, but only certain combinations of chemicals and catheter materials are compatible [18,19]. Catheter coatings impregnated with silver alloy have shown mixed results with no clear efficacy in human patients [20-22]. Prior methods designed to impregnate bacteriophage failed to produce sufficient reduction in biofilm formation.
Therefore, there is a need for new methods of preventing or treating biofilm formation on the surface of medical devices, or for localized therapy of bacterial infection such as in burn therapy.